The emergence of multidrug resistance (MDR) in cancer cells has been a significant impediment to successful cancer chemotherapy treatments because multidrug resistant tumor cells exhibit simultaneous resistance to a number of structurally and functionally unrelated anticancer drugs. Therapeutic strategies to overcome multidrug resistance as well as the adverse side effect that come with chemotherapy treatments may greatly improve the efficacy of chemotherapy treatments. Previously, two different approaches have been proposed and evaluated to treat MDR cancers—the increase of drug dosage and the suppression of cellular resistance to anticancer drugs.
Administration of drugs at high dosage is expected to overwhelm the MDR effect. For most of the nano-sized drug carrier, however, the therapeutic drugs constitute only a minor portion in drug carries in order to minimize the initial drug release in the bloodstream before the drugs reach the cancer cells. The drug content generally cannot exceed 10% in nanoparticles or liposomes. Therefore, large amounts of carriers have to be used to administer a high dose of the anticancer drug to overcome the MDR effect. However, repeated intravenous (IV) and infusion administrations of high doses of low drug loading drug carriers may cause severe toxicity, such as hepatotoxicity, lipotoxicity, neutropaenia, or thrombocytopenia, and will impose a burden for the patients to absorb or excrete the drug carrier materials.
To circumvent this problem, an alternative strategy for MDR cancer treatment is to suppress the activities of the proteins responsible for cellular defense induced by the chemotherapy agents. Small interfering nucleic acids, such as RNA (siRNA)-mediated RNA interference (RNAi) have recently emerged as a potent approach to induce specific silencing of a broad range of genes. Recently, there is a surge of interest in developing platforms for the simultaneous delivery of anticancer drugs as apoptosis inducers and siRNA's as suppressors of cellular defense to enhance chemotherapeutic effects. However, the lack of efficient co-delivery systems limits the potential of the combinatorial therapy of siRNA's and anticancer drugs for MDR cancer therapy. Moreover, a large amount of undesired toxic and non-degradable materials have to be used as a carrier to deliver both the small interfering nucleic acids and anticancer drugs in current delivery systems.
Thus, there is a need in the art for a high drug loading system that co-delivers an anticancer drug with nucleic acids to be used in therapy against cancers, and methods for making them that is efficient in delivering the drugs and that does not use undesired toxic and non-degradable materials as a carrier system for the drugs.